Radiolabeling of [18F]altanserin - a microfluidic approach

Our aim was the optimization of radiochemical parameters for the microfluidic preparation of [(18)F]altanserin. The four main parameters evaluated were (1) precursor concentration, (2) reaction temperature, (3) bolus flow rate through the microreactor and (4) bolus volume.

For the determination of optimal reaction conditions within a flow-through microreactor synthesizer, 5-400 μL of precursor and dried [(18)F]fluoride solution were simultaneously pushed through the temperature-controlled reactor (180-220°C) with defined bolus flow rates of 10-60 μL/min. Radiochemical incorporation yields (RCIYs) were examined using a thin layer chromatography (TLC) set-up and radio- high-performance liquid chromatography (HPLC).

Optimum reaction parameters for the microfluidic set-up were determined as following: 220°C, 5-10 μL/min pump rate per reactant (10-20 μL/min reaction overall flow rate) and 2mg/mL precursor concentration in the reaction mixture. Applying these optimized conditions, RCIYs of 53.7 ± 7.9 were observed for scaled-up preparations. A positive "bolus effect" was observed: applying higher reaction volume resulted in increased RCIYs.

This study proved that the reaction bolus volume is an essential parameter influencing the RCIY of [(18)F]altanserin. A possible explanation is the inhomogeneous distribution within the reaction volume probably caused by diffusion at the bolus interface. This important finding should be considered an important variable for the evaluation of all novel radiotracers labeled using a flow-through reactor device.